Biomarker-driven mechanisms and therapeutic targets for prostate diseases through mendelian randomization and...

Prostate diseases, comprising prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer (PCA), represent substantial public health burdens. This study aimed to clarify biomarker-disease relationships and identify potential therapeutic targets for prostate disorders using a Mendelian Randomization (MR) framework.

We conducted two-sample MR analyses using genome-wide association data. Causal effects were estimated using complementary MR methods. To identify therapeutic targets, MR findings were integrated with DrugBank, protein-protein interaction networks, bulk RNA sequencing, and molecular docking.

Six biomarkers showed causal effects on prostate diseases: URK on prostatitis; GGT and TBIL on BPH; and UCR, PHOS, and BUN on PCA. Functional integration highlighted MPO and TUBB as drug targets for BPH, while docking implicated MET and ATP8B1 in BPH and GATA3 and ENPP3 in PCA. Drug repurposing suggested dexamethasone for BPH and colchicine and metformin for PCA.

This study provides genetic evidence linking biomarkers to prostate diseases and identifies novel druggable targets and repurposing opportunities, offering mechanistic insights and prospects for precision therapy.